The incidence of obesity in the United States and worldwide continues to escalate and with it there is a corresponding increase in the associated problems of cardiovascular disease, diabetes, and other related disorders. Much of the obesity is dietary induced and is correlated with high-fat content in the average Western diet. Though the link between fat intake and obesity has been extensively studied, there is comparatively little known about the mechanisms by which the body recognizes dietary fat and even less known about how these mechanisms correlate and contribute to the regulation of dietary fat intake. We have recently demonstrated that the essential fatty acids provide salient cues to the gustatory system, consistent with this representing the first detailed description of their being a "taste of fat". Moreover, we have shown in preliminary experiments that this fatty acid-mediated inhibition of delayed rectifying K+channels may be a universal system by which the body recognizes dietary fat. The overall aim of this project combining electrophysiology, molecular biology and behavioral assays is to identify and characterize the responsiveness of taste system and its role in helping to shape the dietary preferences of strains of fat-preferring and fat-avoiding rats. To accomplish these goals we will address the following 3 specific aims in these two rat strains: AIM 1: To determine the responsiveness of taste receptor cells from fat-preferring and avoiding rate to fatty acids, their mechanism of action and how this responsiveness correlates with dietary fat preference. This will test the general hypothesis that the differential fat responsiveness in these two strains is due to difference in K+ channel expression and identify the fat responsive elements. AIM 2: To determine the effectiveness of fatty acids as gustatory stimuli. We will use a series of behavioral assays to test the hypotheses that essential fatty acids are recognized by the taste system and that they may enhance the response to other tastants. We will also determine how the differences seen at the taste cell level between rats with different dietary fat preferences is correlated with behavior. AIM 3: To determine the role the taste system may play in helping to shape nutrient (fat) intake. We will analyze eating behavior in the presence of various diets to test the hypothesis that the fatty acid mediated taste cell activation contributes to the control of fat intake. These studies will advance our understanding the mechanisms of fat signaling and their relationship to dietary preferences. Moreover, it may provide insights into a novel therapeutic targets that can be used in the regulation of fat intake and, ultimately, in the control of dietary-induced obesity and its related disorders.